Table 1.

Therapeutic drugs modulating monocytes/macrophages in RA.

Drugs	Immune Target	Clinical Stage	Main Course of Action on Macrophages/Monocytes
Infliximab	TNF	Approved	Neutralization of TNF, apoptosis of monocytes and macrophages in both peripheral blood and synovial fluid.
Adalimumab		Approved
Etanercept		Approved
Golimumab		Approved
Certolizumab pegol		Approved
Tocilizumab	IL-6	Approved	Inhibition of IL-6, apoptosis of monocytes.
Sarilumab		Approved
Olokizumab		Phase III
Clazakizumab		Phase IIb
Vobarilizumab		Phase III
Sirukumab		Phase III
Anakinra	IL-1	Approved	Inhibition of IL-1.
Canakinumab		Phase II
Rilonacept		Phase II
Mavrilimumab	GM-CSF	Phase IIb	Blocking of GM-CSF, inhibition of M1 polarization.
Gimsilumab		Phase I
Otilimab		Phase III
Namilumab		Phase II
Lenzilumab		Phase II
Tofacitinib	JAK1/JAK3	Approved	Blocking of JAK-STAT pathway activity and macrophage-secreted inflammatory factors.
Baricitinib	JAK1/JAK2	Approved
Upadacitinib	JAK1	Approved
Spebrutinib	BTK	Phase II	Blocking of macrophage-secreted TNF-α, nitric oxide and IL-Iβ.
Fenebrutinib		Phase II
Abatacept	CD80/CD86	Approved	Prevention of co-stimulation between APCs and T cells. Inhibition of monocyte differentiation into osteoclasts.
Ustekinumab	IL-12/IL-23	Phase II	Inhibition of IL-12/IL-23.
Guselkumab	IL-23	Phase II	Inhibition of IL-23.
H22 (scFv) -MAP	CD64	Preclinical	CD64+ M1 macrophage apoptosis.
VIB4920	CD40L	Phase II	Blocking the access of macrophages to the synovial tissue.
Clodronate-containing liposomes	Release chlorophosphate	Preclinical	Macrophage depletion.
NI-0101	TLR-4	Phase II	Blocking innate inflammatory responses by blocking TLR-4 activation.
TAK-242	TLR-4	Preclinical	Blocking innate inflammatory responses by blocking TLR-4 activation.